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Cavity Boost Radiation Therapy vs. Observation in Cerebral Metastases After Complete Surgical Resection (C-O-MET)

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ClinicalTrials.gov Identifier: NCT02887651
Recruitment Status : Recruiting
First Posted : September 2, 2016
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf

Brief Summary:
The purpose of this study is to determine whether a local fractionated radiation therapy achieves a better local tumor control after complete surgical metastases resection at 6 month as compared to observation alone. Further it should be evaluated if cognitive functioning and quality of life is similar in both groups.

Condition or disease Intervention/treatment Phase
Cerebral Metastases Surgery Radiation: Cavity boost radiation Phase 2 Phase 3

Detailed Description:

The surgical resection of cerebral metastases as a key element in a multimodal therapeutic concept of brain metastatic patients is included in the common recommendations and international guidelines (level I evidence). These recommendations are based on a series of prospective, randomized and controlled studies which addressed the impact of the surgical metastases resection combined with a whole-brain radiation therapy (WBRT) in comparison to WBRT alone. Achieving local tumor control is the major goal of surgery and local tumor control rate after surgery alone has been addressed in few studies: A prospective, randomized American multicenter study revealed a local recurrence rate of 46% by median follow-up of 43 weeks for patients who underwent surgery alone without an adjuvant radiation therapy. Similarly, the 2-year local recurrence rate after metastases resection alone was 53.1% in a retrospective Korean study and 59% in the prospective, randomized and controlled EORTC 22952-26001 study.

In conclusion, standard surgery alone is not sufficient to achieve local control in about 50% of patients (evidence level I). Therefore, surgery of cerebral metastases is often followed by an adjuvant radiation therapy, which is an important part of a multi-modal therapy. Evidence for an additional adjuvant whole-brain radiation therapy (WBRT) after surgical resection was gained from a first prospective, randomized study in 1998: Patients treated by surgery followed by adjuvant WBRT had a significant lower local in-brain progression rate as compared to patients randomized to surgery alone (46% with a median follow-up of 48 weeks in the observation group vs. 10% with a median follow-up of 43 weeks). This result was recently confirmed by the EORTC 22952-26001 study: The 2-year local in-brain progression rate after surgical resection was reduced by a WBRT from 59% to 27%. But despite the lower local and also lower distant in-brain progression rate, the WBRT had no significant influence on the overall survival. The additional analysis of the quality of life data of the EORTC 22952-26001 study showed, that a WBRT negatively impacts the health-related quality of life with a statistically relevant and clinically significant impairment of the physical functioning (at 8 weeks), cognitive functioning and of the global health status. In conclusion, WBRT after surgery of cerebral metastases significantly reduces the incidence of local recurrences but has no impact on the overall survival and has a significant negative impact on the patient´s quality of life and cognitive function. Therefore, WBRT is not mandatory as adjuvant concept after surgical metastases resection and does not have an additional oncological impact in comparison to observation.

A local fractionated radiation therapy in analogy to the WBRT might achieve a similar local tumor control than observation alone but might be associated with an improved cognitive functioning as compared to WBRT. The purpose of this study is to determine whether a local fractionated radiation therapy achieves a better local tumor control after complete surgical metastases resection at 6 month as compared to observation alone. Further it should be evaluated if cognitive functioning and quality of life is similar in both groups.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cavity Boost Radiation Therapy vs. Observation in Cerebral Metastases After Complete Surgical Resection
Study Start Date : October 2016
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2020

Arm Intervention/treatment
No Intervention: observation
patients in the observation arm receive no adjuvant local radiation therapy after complete surgical resection of a cerebral metastasis
Active Comparator: cavity boost radiation therapy
patients in the intervention arm receive an adjuvant local radiation therapy (cavity boost radiation therapy: 10 x 3 Gy ad 30 Gy; clinical target volume (CTV): resection cavity plus surrounding 5 mm; planning target volume (PTV): CTV + 1mm)
Radiation: Cavity boost radiation
Cavity boost radiation therapy with 10 x 3 Gy for patients suffering from complete resected cerebral metastases




Primary Outcome Measures :
  1. Local tumor control of resected metastases at 6 month [ Time Frame: 6 month ]
    Primary outcome measure is the local tumor control of resected metastases after local cavity boost radiation therapy or observation at 6 month


Secondary Outcome Measures :
  1. Local tumor control of resected metastases at 12 and 18 month [ Time Frame: 12, 18 month ]
    Secondary outcome measure is the local tumor control of resected metastases after local cavity boost radiation therapy or observation at 12 and 18 month

  2. Distant tumor control of resected metastases at 6, 12 and 18 month [ Time Frame: 6, 12 and 18 month ]
    Secondary outcome measure is the distant tumor control at 6, 12 and 18 month

  3. Incidence of leptomeningeal carcinosis [ Time Frame: 6, 12 and 18 month ]
    Secondary outcome measure is the incidence of a leptomeningeal carcinosis at 6, 12 and 18 month

  4. Eortc qlq bn20 questionaire [ Time Frame: 6 weeks, 3, 6, 9 12, 15, 18, 21, 24 month ]
    Secondary outcome measure is the patients quality of life at 6 weeks, 3, 6, 9 12, 15, 18, 21 and 24 month as assessed by the Eortc qlq bn20 questionaire

  5. Eortc qlq c30 questionaire [ Time Frame: 6 weeks, 3, 6, 9 12, 15, 18, 21, 24 month ]
    Secondary outcome measure is the patients quality of life at 6 weeks, 3, 6, 9 12, 15, 18, 21 and 24 month as assessed by the Eortc qlq c30 questionaire

  6. Mini-Mental State Examination (MMSE) [ Time Frame: 6 weeks, 3, 6, 9 12, 15, 18, 21, 24 month ]
    Secondary outcome measure is the patients neurocognitive functioning at 6 weeks, 3, 6, 9 12, 15, 18, 21 and 24 month as assessed by the MMSE,

  7. Hopkins Verbal Learning Test (HVLT) [ Time Frame: 6 weeks, 3, 6, 9 12, 15, 18, 21, 24 month ]
    Secondary outcome measure is the patients neurocognitive functioning at 6 weeks, 3, 6, 9 12, 15, 18, 21 and 24 month as assessed by the Hopkins Verbal Learning Test (HVLT),

  8. Controlled Oral Word Association (COWA) [ Time Frame: 6 weeks, 3, 6, 9 12, 15, 18, 21, 24 month ]
    Secondary outcome measure is the patients neurocognitive functioning at 6 weeks, 3, 6, 9 12, 15, 18, 21 and 24 month as assessed by the Controlled Oral Word Association (COWA)

  9. Test and Trail-Making Test (TMT) A & B [ Time Frame: 6 weeks, 3, 6, 9 12, 15, 18, 21, 24 month ]
    Secondary outcome measure is the patients neurocognitive functioning at 6 weeks, 3, 6, 9 12, 15, 18, 21 and 24 month as assessed by the Test and Trail-Making Test (TMT) A & B



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • histologically confirmed metastasis of carcinoma (except small cell carcinoma) or malignant melanoma
  • 1-3 metastases in the preoperative MRI
  • Karnofsky Performance Status (KPS) ≥ 70
  • Age > / = 18 years
  • Recursive partitioning analysis (RPA) 1-2
  • life expectation ≥ 6 months
  • no previous irradiation of the brain
  • MRI examinations possible
  • start of the radiation therapy possible within 6 month after surgery
  • informed consent

Exclusion Criteria:

  • confirmation of residual tumor in the postoperative MRI within 72 hours after surgery
  • dementia or disease of central nervous system with a higher risk or radiogenic toxicity
  • contraindication for MRIs or lack of acceptance for a MRI
  • Glasgow Coma Scale < 12
  • Age < 18 years
  • KPS < 70, RPA 3
  • life expectation < 6 months
  • therapeutic previous irradiation of the brain
  • no histological confirmation of carcinoma metastases or malignant melanoma metastases
  • cerebral metastases of small cell cancer, undifferentiate neuro-endocrine carcinoma, lymphoma, leucemia, sarcoma or germ cell tumor
  • leptomeningeal carcinosis
  • distance of the cerebral metastasis to the optic system or radiation sensible brain parts < 10 mm
  • distance to further metastases < 3 cm
  • metastases of the brain stem, Di- or Mesencephalons, Pons oder Medulla oblongata
  • bone marrow dysfunction
  • contrast agent allergy
  • pregnancy
  • no informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02887651


Contacts
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Contact: Marcel A. Kamp, MD 0049 - 211 - 81 - 07461 marcelalexander.kamp@med.uni-duesseldorf.de

Locations
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Germany
Heinrich-Heine-University Recruiting
Düsseldorf, NRW, Germany, 40225
Contact: Marcel A. Kamp, MD    0049-211-81-07461    marcelalexander.kamp@med.uni-duesseldorf.de   
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
Investigators
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Principal Investigator: Michael Sabel, Prof. Dr. Department of Neurosurgery
Principal Investigator: Wilfried Budach, Prof. Dr. department of radiation oncology

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Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT02887651    
Other Study ID Numbers: 5405
First Posted: September 2, 2016    Key Record Dates
Last Update Posted: July 24, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Heinrich-Heine University, Duesseldorf:
cerebrale metastases
radiotherapy
surgery
complete surgical resection
resection
cavity boost radiation therapy
observation
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms, Second Primary
Neoplastic Processes
Neoplasms
Pathologic Processes